1. Field of the Invention
The present invention relates to the extraction of a small ligand such as molecular oxygen from a ligand-containing environment by the utilization of carrier compounds immobilized on a solid phase.
2. Description of the Relevant Art
Oxidative damage to beverages, foods and edible oils is a well-documented problem. See, Richardson et al., ed., Chemical Changes in Food During Processing, 1985, AVI Publishing Company, Westport, Conn. The principal effects of this damage are on proteins, edible oils, and fats, although carbohydrates are also affected. Unsaturated fats contain double bonds which undergo free radical reactions in the presence of oxygen, with the concomitant formation of lipid hydroperoxides. These hydroperoxide products are themselves highly reactive species which can in turn react with carbohydrates and proteins present in the food product, forming complex polymeric products. These degradation products adversely affect color, flavor and nutritional value of the products in which they occur. In some cases, these degradation products may be toxic or carcinogenic.
Prior to the present invention, several methods for controlling oxygen in food products and packages have been developed. However, each of these has shortcomings. Vacuum packing and gas sparging are expensive processes which remove oxygen but also expel the volatile oils which contribute to many of the desirable flavors and odors of a product. Hot-fill packaging reduces the level of oxygen present in food but can also accelerate the oxidation reaction itself, thereby exacerbating the problem. Antioxidant food additives such as ascorbic acid, tocopherol (vitamin E) and BHA have demonstrated effectiveness to reduce oxygen. However, they can only be added safely in limited quantities and they defeat the effort to deliver foods naturally.
Of more pertinence to the present invention, various forms of oxygen-absorbing materials have been incorporated into food and other product packaging to lower residual oxygen levels after a package has been sealed. See, for example, U.S. Pat. No. 4,756,436, which discloses the use of an iron powder absorbent incorporated in a bottle cap; U.S. Pat. Nos. 4,421,235 and 4,287,995, which disclose bottle caps and packets which contain various oxygen absorbers, such as copper amine complexes; and U.S. Pat. Nos. 4,667,814; 4,579,223; 4,092,391; 3,586,514; Japanese Patent No. 62122569; and European Patent No. 142903, which disclose other forms of oxygen absorbent packaging. Oxygen absorbent packaging is also disclosed in various literature references, including Roessel (1988) Misset's Pakblad 10:42-46; Wolpert (1987) Paper Film and Foil Converter 61:64-66; Packaging (USA) June 1988, p. 83; Food Processing (Chicago) 49:58-59 (1988); Business Week, June 27, 1988, pp. 90-91; and Food Packaging (1988) 49:22. The latter four references refer to the use of Longlife.TM. in food packaging. Longlife.TM. is the tradename for oxygen absorbers according to the present invention.
The use of oxygen-absorbent materials in food packaging has been limited by the tendency of such materials to prematurely bind oxygen, i.e., prior to their incorporation in the packaging. To avoid such premature oxygen-binding, it is necessary to either perform packaging operations in an oxygen-free environment, prevent oxygen exposure in some other way (e.g., store and manipulate the materials under a protective barrier), or drive-off bound oxygen after the material is incorporated in the packaging and before the package is sealed. Each of the approaches significantly complicates the packaging operation and is therefore undesirable. It would thus be desirable to utilize oxygen absorbent compositions which would be substantially incapable of binding oxygen during the packaging operation but be activatable after the package is sealed. This would allow packaging operations to be performed in an oxygen-containing environment without loss of activity by the absorbent.
U.S. Pat. Nos. 4,536,409 and 4,702,966, and European Patent Application No. 83826, disclose an activatable oxygen-absorbing system which employs potassium sulfite as the absorbent. Potassium sulfite is able to bind oxygen only when wet. The packaging system employs a gas-permeable membrane which is water-permeable only at elevated temperatures. Thus, the absorbent may be activated by simultaneous exposure to heat and water. Although functional, this system suffers from certain limitations. For example, the system is not suitable for heat-labile products which cannot be exposed to elevated temperatures. Additionally, the potassium sulfite can adversely affect the flavor and odor of a packaged food product.
For these reasons, it would be desirable to provide alternate oxygen-absorbing compositions, systems, and methods. Such compositions should have a high oxygen-binding capacity, should be compatible with most or all comestibles and other oxygen-sensitive products, should be usable in environments containing other gases (such as carbon dioxide), should be usable in wet and dry environments, and should be economic to employ. In particular, the oxygen-absorbing systems and methods should provide for selective activation of the absorbent composition, including activation without the use of heat.
A variety of naturally-occurring metalloproteins, including hemoglobin, myoglobin, hemocyanin, and hemerythrin, are capable of reversibly binding oxygen and transporting oxygen from a permeable membrane to a site within an organism at which the oxygen is needed. In hemoglobin, for example, oxygen is reversibly bound to ferrous [Fe(II)] porphyrins incorporated in the protein. Oxidized, ferric hemoglobins are unreactive to molecular oxygen. The properties of hemoglobins, hemerythrins, and hemocyanins have been the subjects of numerous studies, as documented in, e.g., Bonaventura, et al., Symposium on Respiratory Pigments, 20 J. Am. Zool. 20:7 (1980) and 20:131 (1980).
The oxygen binding capabilities of such metalloproteins have been utilized to extract oxygen from air and other fluids. Miller, U.S. Pat. No. 3,230,045 discloses the use of an oxygen binding chromoprotein such as hemoglobin to separate oxygen from other gases. The chromoproteins are kept moist or in solution and are absorbed on or bound to filter paper. An electrolyte such as sodium chloride may also be present. The filter paper is alternately exposed to air (the carrier absorbs oxygen) and vacuum, which removes the bound oxygen. Bonaventura et al., U.S. Pats. No. 4,427,416, and 4,343,715, also use naturally-occurring oxygen carriers to extract oxygen from fluids. The metalloproteins are insolubilized at high concentrations by entrapment and/or covalent linkage to a polyurethane matrix or similar, flexible support in states that are capable of reversibly binding oxygen. The material disclosed in these patents, generally known as "hemosponge" since it usually incorporates hemoglobin or another heme-type protein, is capable of extracting oxygen from various fluid environments. However, the rate of extraction is less than that which may be desired for many applications which involve a high rate of oxygen use. Further, these disclosures utilize chemical regeneration of the oxidized carrier compounds, with, e.g., ferricyanide solutions, which, in applications which require large amounts of oxygen, present considerable supply and waste disposal problems. Release of bound oxygen from the "hemosponges" requires either chemical oxidation of the carrier compound with the concomitant supply and waste disposal problems or various methods for pressing the hemosponge, which require pumps, vacuums, and the like which use substantial quantities of energy.
A variety of transition metal complexes with mono-, bi-, and multi-dentate chelates are also capable of reversibly binding oxygen. Such artificial oxygen carriers and their properties in solutions have been described by a number of researchers. For example, Brault, et al., Biochemistry 13:4591 (1974), discloses the preparation and properties of ferrous deutero- and tetraphenyl- porphyrins in various organic solvents. Castro, Bioinorganic Chemistry 4:45-65 (1974), discloses the synthesis of hexa- and penta-coordinate iron porphyrins, which are models for the prosthetic groups of active sites of certain cytochromes and other heme proteins. Other iron-containing transition metal compounds which may reversibly bind oxygen are described by Chang, et al., J. Am. Chem. Soc. 95:5810 (1973).
Numerous cobalt, manganese, and copper compounds also exhibit reversible oxygen binding. For example, Crumbliss, et al., Science 164:1168-1170 (1969) disclose Schiff base complexes of Co(II) which form stable complexes with oxygen species in solution. See also: Crumbliss, et al. J. Am. Chem. Soc. 92:55 (1970) (monomeric cobalt complexes of oxygen); Dufour, et al., J. Mol. Catalysis 7:277 (1980) (Catalysis of oxidation of simple alkyl-substituted indoles by Co(II), Co(III), and Mn(III) meso-tetraphenyl porphyrins via a ternary porphyrin-indole-oxygen complex); Brinigar, et al., J. Am. Chem. Soc. 96:5597 (1974) (effect of solvent polarity on reversible oxygenation of several heme complexes prepared by reduction with sodium dithionite or a mixture of palladium black and calcium hydride); Hill, U.S. Pat. No. 4,442,297 (absorption of gases using manganese compounds); Simmons, et al., J. Chem. Soc. Dalton Trans. 1827 (1980) (reversible coordination of oxygen to copper / (I) complexes of imidazole derivatives).
A variety of devices and methods utilizing such synthetic transition metal oxygen-carrier compounds have been devised for extraction of oxygen from air. For example, Warne, et al., U.S. Pat. No. 2,217,850, disclose the reaction of oxygen in air with solids of cobaltous hexamine salts to synthesize, on a large scale, peroxo-cobalt amine solids, followed by removal of the solution, and separate chemical regeneration of the oxygen and the starting cobalt hexamine salts. Fogler, et al., U.S. Pat. No. 2,450,276 utilize a solid cobaltous compound of a tetradentate Schiff base ligand to extract oxygen from air by alternately cooling a bed of the solid carrier compound, which absorbs oxygen from the air, and heating the oxygenated carrier compound to release bound oxygen. This process is accompanied by severe decomposition of the carrier compound. Iles, et al., U.S. Pat. No. 4,165,972 discloses an apparatus for alternately heating and cooling alternate beds of carrier compound to absorb oxygen from air into cooled beds of carrier and expel oxygen into a second gas handling system by heating the bed of carrier compound.
Roman, U.S. Pat. No. 4,542,010, discloses a method for producing oxygen and nitrogen using a porous, hydrophilic membrane support containing a solution of a transition metal oxygen carrier in a non-aqueous solvent. This device serves as a facilitated diffusion membrane. Oxygen bound to the carrier diffuses from a first permeable membrane contacting air to a second membrane where the oxygen is released from the carrier. Thus, the permeability of oxygen through the membrane is increased by the reversible binding of oxygen to the organometallic carrier compound. Loading and unloading of oxygen from the liquid membrane is accomplished by a combination of temperature and/or pressure differentials. One drawback to this process is that oxygen generated using this device is costly, since the temperature and/or pressure differentials required to load and unload the oxygen carriers require large energy inputs. In addition, both sides of the membranes must remain saturated with solvent in order for the membrane to function, significantly adding to the cost and complexity of the device.
It is now well understood that many such transition metal-based carriers typically have a lower valence state, i.e., Mn(II), Fe(II), Co(II) or Cu(I) in which the carrier is capable of reversibly binding molecular oxygen under appropriate conditions; and a higher valence (more oxidized) state, e.g., Mn(III), Fe(III), Co(III), or Cu(II), in which binding of molecular oxygen is essentially absent. Most of the known methods for extracting oxygen from air using such transition metal carrier compounds are dependant upon the carrier compound remaining in the lower valence state. Molecular oxygen is absorbed from sources with a relatively high concentration (and hence chemical activity) of oxygen and reversibly bound to the carrier compound. The oxygen desorbs when the carrier compound is exposed to an environment in which the chemical activity of oxygen is lower, e.g., low oxygen partial pressures or elevated temperatures. Extraction processes may be carried out by exposing the carrier compounds to alternating environments of higher and lower oxygen activity, e.g., alternating partial pressure of oxygen or alternately low and high temperatures. The carrier compound may actually be used to carry oxygen from the feedstock environment to the delivery environment by diffusion or by pumped circulation.
Some types of artificial transition metal carrier complexes have been used in or suggested for use in devices for extraction, absorption, and generation of oxygen from fluid media. For example, Roman, U.S. Pat. Nos. 4,451,270 and 4,452,010, discloses Schiff base complexes of metals in an oxygen selective, permeable membrane and extraction system. The carriers include cobalt complexes of linear and macrocyclic tetradentate, linear pentadentate, and bidentate Schiff base chelates in primarily non-aqueous, Lewis base solvents. Hill, U.S. Pat. No. 4,442,297, uses phosphine complexes of Mn(II) in dehydrated solvents to purify nitrogen gas by extracting impurities including molecular oxygen. Sievers, U.S. Pat. No. 4,514,522, discloses oxygen sorbents comprising linear, tetradentate ketoamine complexes bound to porous polymers. Gagne, U.S. Pat. No. 4,475,994, uses cobalt complexes of unknown stoichiometry in a mixed solvent at high pH to transport electrochemically generated superoxide ions across a fluid membrane. Bonaventura et al., U.S. Pats. Nos. 4,602,383; 4,609,987; and 4,629,544, disclose a variety of metalloporphyrins, in combination with Lewis bases, in aqueous, non-aqueous, and water-immiscible solvents and their use to electrochemically separate oxygen from fluids.
Oxygen carrier compounds, including cobalt complexes of some linear, pentadentate polyamines, and their properties have been extensively reviewed and tabulated. Niederhoffer, et al., Chem. Rev. 84:137-203 (1984). More detailed investigations of cobalt complexes of some linear, pentadentate polyamines have been reported in a series of articles by Harris, et al., and Timmons, et al.: Harris, et al., Inorg. Chem. 17:889 (1978); Timmons, et al., Inorg. Chem. 17:2192 (1978); Timmons, et al., Inorg. Chem. 18:1042 (1979); Timmons et al., Inorg. Chem. 18:2977 (1979); Harris, et al., Inorg. Chem. 19:21 (1980); and Timmons, et al., Inorg. Chem. 21:1525 (1982). The use of transition metal complexes of polyalkylamines in electrochemical or other oxygen extraction and generation processes is disclosed in co-pending, commonly assigned U.S. patent application Ser. No. 018,891, filed Feb. 25, 1987.
Incorporation of oxygen carriers into polymeric matrices has been achieved by several workers in the field. Wang (in Oxygenases, Hayaishi, ed., 502-511, 1962, Academic Press, New York) has described incorporation of heme into a polystyrene matrix. This complex was demonstrated to be functional in reversible oxygen binding. Subsequently, immobilization of heme and synthetic heme analogs has been carried out on polystyrene, vinyl copolymers, polymethacrylate, polyvinylpyrrolidone and dextran. See, Ledon, et al., J. of Organometallic Chem. 165:C25 (1979); Gitzel, et al., Polymer 27:1781 (1986); Wohrle, et al., Chem. 187:2081 (1986); Shigehara, et al., Macromolecules 14:1153 (1981); Nishide, et al., Macromolecules 19:494 (1986), Macromolecules 20:417 (1987), Macromolecules 20:1913 (1987), and Macromolecules 20:2312 (1987c).